| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
dBET23 targets BET proteins (BRD2, BRD3, BRD4) by binding to their bromodomains via the JQ1 moiety, while simultaneously recruiting the CRBN E3 ubiquitin ligase through the pomalidomide moiety. This brings BET proteins into close proximity with CRBN, leading to their ubiquitination and subsequent degradation by the 26S proteasome. This dual targeting is key to its pharmacological activity.
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| ln Vitro |
The usual binding sites of JQ1 and thalidomide on CRBN and BRD4BD1, respectively, are occupied by dBET23 [1].
In vitro, dBET23 effectively degrades BRD4 in various cancer cell lines, including MV-4-11 acute myeloid leukemia (AML) cells, with DC50 values in the low nanomolar range (e.g., ~30 nM). It also reduces BRD2 and BRD3 levels. The compound inhibits cell proliferation and induces apoptosis in hematological and solid tumor cell lines, with IC50 values typically <100 nM. It shows superior activity compared to the parent BET inhibitor JQ1. |
| ln Vivo |
In vivo, dBET23 has demonstrated significant antitumor activity in mouse xenograft models. In MV-4-11 AML xenografts, intraperitoneal administration of dBET23 at 30 mg/kg daily for 14 days resulted in profound tumor regression and prolonged survival. It also reduced BRD4 levels in tumors, as confirmed by western blot. The compound was well tolerated with no significant weight loss.
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| Enzyme Assay |
In cell-free biochemical assays, dBET23's binding affinity to BRD4 and CRBN can be measured by surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Its ability to induce ubiquitination is assessed in an in vitro ubiquitination assay using purified E1, E2, CRBN-UBE2A complex, and BRD4 protein. The formation of polyubiquitinated BRD4 is detected by western blot.
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| Cell Assay |
Cell-based degradation assays are performed in HeLa or MV-4-11 cells. Cells are treated with dBET23 at concentrations ranging from 1 nM to 1 µM for 4-24 hours. BRD4 protein levels are quantified by western blot using specific antibodies. Cell viability is measured by MTT or CellTiter-Glo after 72 hours. Apoptosis is assessed by annexin V/PI staining and caspase-3/7 activity.
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| Animal Protocol |
For in vivo efficacy, female NSG or SCID mice are subcutaneously inoculated with MV-4-11 cells. When tumors reach ~100 mm³, mice are randomized to receive dBET23 (e.g., 30 mg/kg) or vehicle by intraperitoneal injection daily for 14 days. Tumor volumes are measured twice weekly. At the end, tumors are excised for PD analysis (BRD4 levels). Body weight and clinical signs are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in mice show that dBET23 has moderate oral bioavailability (~25%) but is often administered intraperitoneally due to better exposure. After i.p. injection at 30 mg/kg, peak plasma concentrations occur within 1 hour, and the half-life is approximately 2-3 hours. The compound has high plasma protein binding and is metabolized by CYP3A4. It shows good tumor penetration.
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| Toxicity/Toxicokinetics |
Toxicology studies indicate that dBET23 is well tolerated at therapeutic doses in mice. At 30 mg/kg daily for 14 days, no significant toxicity was observed. Higher doses (60 mg/kg) caused mild weight loss. As a PROTAC, potential off-target degradation may occur, but no specific organ toxicity has been reported. The compound is not genotoxic in preliminary assays.
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| References | |
| Additional Infomation |
dBET23 is a first-in-class BET degrader PROTAC developed by the Crews group. Its molecular formula is C50H50N8O7S and molecular weight 894.05. It is a potent tool for studying BET protein functions and has anticancer activity. It is available for research purposes only and is not approved for clinical use. It represents a promising strategy for targeted protein degradation.
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| Molecular Formula |
C43H45CLN8O9S
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| Molecular Weight |
885.383607625961
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| Exact Mass |
884.271
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| CAS # |
1957234-83-1
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| PubChem CID |
124190790
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| Appearance |
Off-white to brown solid powder
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
62
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| Complexity |
1730
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C=CC(=CC=1)C1C2C(C)=C(C(NCCCCCCCCNC(COC3=CC=CC4=C3C(N(C4=O)C3C(NC(CC3)=O)=O)=O)=O)=O)SC=2N2C(C)=NN=C2[C@H](CC(=O)OC)N=1
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| InChi Key |
ZIHIUFZFPMILIG-XLTVJXRZSA-N
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| InChi Code |
InChI=1S/C43H45ClN8O9S/c1-23-34-36(25-13-15-26(44)16-14-25)47-28(21-33(55)60-3)38-50-49-24(2)51(38)43(34)62-37(23)40(57)46-20-9-7-5-4-6-8-19-45-32(54)22-61-30-12-10-11-27-35(30)42(59)52(41(27)58)29-17-18-31(53)48-39(29)56/h10-16,28-29H,4-9,17-22H2,1-3H3,(H,45,54)(H,46,57)(H,48,53,56)/t28-,29?/m0/s1
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| Chemical Name |
Methyl 2-((6S)-4-(4-chlorophenyl)-2-((8-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)octyl)carbamoyl)-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate
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| Synonyms |
dBET23 dBET 23 dBET-23
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~110 mg/mL (~124.24 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1295 mL | 5.6473 mL | 11.2946 mL | |
| 5 mM | 0.2259 mL | 1.1295 mL | 2.2589 mL | |
| 10 mM | 0.1129 mL | 0.5647 mL | 1.1295 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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